1. Field of the Invention
The invention is in the field of sensor technology and relates to an implantable, wirelessly readable biosensor and to a sensor arrangement equipped with such a biosensor.
2. Description of the Related Art
A wide variety of an analytical methods and the necessary device technology therefore exists for detecting the presence of analytes and determining the concentrations thereof in bodily fluids, such as blood. In general, fluid samples are collected, which optionally may be specially conditioned and then supplied to the analysis. The spectrum ranges from simple test strips, which indicate the presence and the concentration of a specific substance (such as glucose) for example by a color change, to complex analyses in specialized laboratories. A key disadvantage of these methods is that samples are collected only a certain (discrete) times and are then analyzed in a more or less complex manner. Particularly with laboratory analyses, additionally the time period between sampling and the availability of the result is usually quite long. In this way, continuous measurements are not possible with these methods.
Often, continuous measurement is desirable, particularly if the measured values are to be used for managing medical devices. By way of example of a disease where continuous measurement is advantageous Diabetes mellitus shall be mentioned. Diabetes mellitus is a wide-spread disease with approximately 250 million cases worldwide, which corresponds to approximately 6% of the worldwide population. Complications and secondary diseases frequently occur in connection with Diabetes mellitus. One example of this is heart disease, which occurs with greater frequency in people with Diabetes mellitus. The therapy of Diabetes mellitus usually is performed by administering insulin, for which a measurement of the blood sugar level is required. The more frequently the blood sugar level is measured, the more efficiently the therapy can be. Automatic insulation administration, for example using insulin pumps, requires a continuous measurement of the blood sugar level in order to enable optimized insulin dosages that are in keeping with the patient's needs.
Furthermore, continuous monitoring of the concentrations of enzymes, hormones, marker molecules, pH values, or of glucose concentrations, is desirable in order to detect pathological changes at an early stage and be able to initiate the necessary therapies.
For this reason, biosensors have attained great importance in the detection of enzymes, hormones, marker molecules, pH values, or glucose concentrations. Chemical and biological sensors are based on the fundamental principle of selectively converting the concentration or the presence of a certain substance into the change of a physical variable, which then can be measured electrically, for example. These physical variables, for example, can be the wavelength of absorbed or emitted light, pressure, viscosity, mass, or also electric variables such as currents, voltages, or impedances.
One possibility for the implementation of sensors are hydrogels. Hydrogels are special polymers, which are able to absorb a solvent, for example water, in a volume that is several times that of their own. This property is created by linking the polymer molecules into a three-dimensional network, into which the solvent molecules (such as water) can become incorporated. Hydrogels can be designed such, for example, that they respond to the change of the concentrations of certain ions (such as the pH value) or certain substances (such as glucose or hormones) with relatively large volume changes. It is also possible to specifically embed compounds that have an affinity for certain substances (such as concanavalin A for glucose) in order to influence in this way the properties of the hydrogel as a function of the concentration of this substance. Beyond the volume change, during the incorporation of the solvent, for example, the viscosity, density, and/or optical and electric properties of the hydrogels can also change. Due to this behavior, hydrogels are suited as a basis for biosensors and chemical sensors. The measurement performed relates to the change of a certain property of the hydrogel (for example the viscosity thereof) in order to determine a concentration of the substance to be determined.
A person skilled in the art is furthermore familiar with so-called SAW (SAW=Surface Acoustic Wave) sensors. SAW sensors in general comprise a piezoelectric substance, to the surface of which so-called interdigital electrodes (IDT=Inter Digital Transducer) are applied. If an AC voltage is applied to an IDT (“input IDT”), acoustic surface waves are generated by way of the inverse piezo effect, which can propagate across the surface of the substrate. These surface waves can be reflected on one or more acoustic reflectors (such as an IDT) and then generate an AC voltage in the input IDT by way of the piezo effect. For example, if an AC voltage pulse is coupled into the input IDT via an antenna, it is converted into an acoustic wave package, which after reflection on the acoustic reflector generates an AC voltage pulse in the input IDT, which is emitted via said antenna, similar to an echo. No additional energy is required for returning this echo. SAW sensors can be configured as delay lines or as so-called one-port resonators and can be operated with frequencies from approximately 30 MHz to more than 10 GHz.
The propagation of the acoustic wave on the surface of the substrate is influenced by different factors, such as the mechanical stress in the substrate, the temperature, the ground layer on the surface, or the acoustic coupling to the ambient medium. As a result of these influences, among other things the propagation velocity of the acoustic surface waves or the attenuation thereof changes, thereby changing the properties of the echo, for example the travel time or amplitude.
Due to these properties, it is possible by means of SAW sensors to implement purely passive, wirelessly readable sensors for different physical variables, which can be polled using a high-frequency electromagnetic pulse, comparable to a radar pulse. The echo received contains the information about the measured value.
SAW sensors can be used as pressure sensors, for example. To this end, the substrate is applied onto a membrane, for example, whereby it is slightly deflected. This deflection can also be achieved in that the force is transmitted from the membrane via a tappet to the suitably supported substrate. Due to the deflection of the substrate, mechanical stresses develop therein, which influence, for example, the propagation velocity of the acoustic wave. As a result, the resonant frequency of the SAW sensor or the phasing of the echo relative to the exciting pulse changes as a function of the mechanical stress, and consequently as a function of the pressure to be measured.
SAW sensors are likewise well-suited for measuring the viscosity of fluids. Here, primarily SAW arrangements are used which operate based on acoustic shear waves (SH-waves). Shear waves have the advantage that acoustically they couple to the fluid only via the viscosity and therefore the attenuation of the surface wave by the adjoining fluid is relatively low. The penetration depth (d) of the surface wave into the fluid depends on the viscosity (η) thereof, the density (ρ) thereof, and the frequency of the surface wave (ω):
  d  =                              2          ⁢          η                          ω          ⁢                                          ⁢          ρ                      .  
Coupling of the acoustic wave into the fluid therefore effectively results in mass loading of the surface, as a result of which the propagation velocity of the acoustic surface wave changes, and also in an attenuation of the wave. These effects can be expressed by acoustic impedance (Za) of the fluid, which likewise depends on the viscosity (η), density (ρ) and frequency (ω)Za=√{square root over (ωρη)}.
As a result, the resonant frequency of the SAW sensor, the phasing of the echo relative to the exciting pulse, or the amplitude of the echo changes as a function of the viscosity of the coupled fluid.
SAW sensors are also suited for measuring conductivities and impedances. For this purpose, the ports of one of the acoustic reflectors on the surface of the SAW sensor are electrically connected to the impedance to be measured, for example electrodes disposed in a defined manner in a fluid. This acoustic reflector is thereby loaded by the electric impedance (Z=R+jX) of the electrode arrangements. As a result, the amplitude and phasing of the echo of this reflector change as a function of the magnitude and phase of the electric impedance of the electrode arrangement, which is influenced both by the electric conductivity of the fluid and by the dielectric properties thereof. The decay behavior of the SAW sensor is also influenced by the load impedance, for example the decay time constant thereof. In this way, the electric properties of the fluid, for example the conductivity or dielectric constant thereof, can be measured by the determination of the parameters of the echoes received.
SAW sensors according to the principles described have already proven useful in industrial applications, for example as tire pressure sensors or oil quality sensors.
As continuously measuring methods, applications based on SAW sensors are known in which the mass accumulation of specific substances is measured. To this end, the surface of the SAW sensor is coated with a selective material, on which the analyte accumulates. The increase in mass on the surface of the SAW sensor is measured using generally known methods and is used to determine the presence and concentration of the analyte. A frequent disadvantage of this method is that the selective coating ages, becomes contaminated, or the absorption of the analyte is not reversible, so that after a certain usage period the measurement is not longer possible with sufficient accuracy and the SAW sensors have to be replaced.
In order to overcome the disadvantage of a short usage period, arrangements are known which operate based on hydrogels. For example, the viscosity of a hydrogel changes upon the penetration of an analyte (such as glucose) into the polymer matrix. The advantage is that this process reversible. With a suitable arrangement, a variable concentration balance develops between the test fluid (hydrogel) and the surrounding area. By measuring the viscosity change, the concentration of the analyte in the sample fluid can be determined (affinity viscosimetry). For example, the viscosity can be measured by the flow resistance over a capillary through which fluid flows. The disadvantage here is that a flow in the sensitive fluid (or hydrogel) must be driven and that the sensitive fluid is consumed in some arrangements. These methods are primarily suited for laboratory measurements. Arrangements in which the viscosity is determined by way of the oscillation behavior of a bending beam enclosed by the hydrogel are not associated with this disadvantage. However, a relatively large amount of energy is required for the excitation of the oscillations of the bending beam, the measurement thereof, and the transmission of the measured values via a telemetry connection, so that the service life and the size of an implantable sensor according to this principle are determined by the battery capacity thereof. Otherwise, energy must be transmitted from the outside for operating the sensor, wherein the sensor then has to comprise means for receiving and storing this energy.
Furthermore arrangements are known which utilize the volume changes of hydrogels by the incorporation of an analyte for determining the concentration. The hydrogel is then provided in a capsule that is closed with a firm semi-permeable membrane. The swelling of the hydrogel effects the pressure change in this capsule, which is measured by means of any arbitrary pressure pickup. Likewise, the osmotic pressure developing as a result of the difference in concentrations inside and outside the capsule can be used for determining the concentration of the analyte. The signals of the pressure pickup are processed in the sensor by measuring electronics and actively transmitted via a telemetry connection. The energy required for this again has to be provided by a battery or by energy transmission. Other known implantable sensors used for determining the concentration of an analyte, for example in the form of a stent, also have the disadvantage that they require a battery or a possibility for energy transmission for operating the measuring electronics and for active telemetry.